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Planar cell polarity

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Cartoon representation of Planar Cell Polarity in fly wing hair cells and mouse paw hair cellsFigure 1. (A and B) Drosophila cuticular wing hair cells of the adult wing. Wing hairs point distally (to the right) in wild-type (WT) animals (A) but lose orientation in PCP mutants (fz) (B). (C and D) Hairs on the mouse paw point away from the body (pointing up) in WT (C) but grow in a swirling pattern in PCP mutants (fz6) (D). Inspired by the work of Paul Adler (A and B) and Guo et al. (2004) (C and D).

Planar Cell Polarity (PCP) is the protein mediated signaling that coordinates the orientation of cells in a layer of epithelial tissue. Of examples of mature PCP oriented tissue are the stereo-cilia bundles in the inner ear,[1] motile cilia of the epithelium,[2] and cell motility in epidermal wound healing.[3] Additionally, PCP is known to be crucial to major developmental time points including coordinating convergent extension during gastrulation and coordinating cell behavior for neural tube closure.[4] Cells orient themselves and their neighbors by establishing asymmetric expression of PCP components on opposing cell members within cells to establish and maintain the directionality of the cells. Some of these PCP components are transmembrane proteins which can proliferate the orientation signal to the surrounding cells.[5]

Table of Contents

  1. Introduction
  2. Table of Contents
  3. History of Planar Cell Polarity (PCP) Research
  4. Core Planar Cell Polarity Components
  5. Canonical Vs. Non-Canonical Wnt Pathways and PCP
  6. Cross Protein Interactions to Establishing PCP Asymmetry
  7. References
  8. See Also:

History of Planar Cell Polarity (PCP) Research

Planar cell polarity was first described in insects and then further defined in fruit flies (Drosophila melanogaster). Some of the earlier work describing gene controlled polarity of fly wings was published by D. Gubb and A. García-Bellido back in 1982 describing how the mutation of some genes resulted in a morphology change in the cuticle orientation on the fly body.[6]  The history of the PCP pathway as it was expanded by fly genetics work, which lead to the interesting names for PCP components like Frizzled, Vang-gogh, and Disheveled. These are typical nomenclature for new genes discovered in flies, which are often based on the description of the visual presentation of the mutant flies for each gene. Early PCP research focused on its role in embryology and genetics, but the discovery that PCP proteins were localized asymmetrically within the cell pushed the topic into the world of cell biology.[5]

As of 2014, there was a surge in interest in the Planar Cell Polarity pathway after the conserved PCP genes were found to be involved in important vertebrate processes vertebrate gastrulation, mammalian ear patterning and hearing, and neural tube closure.[5] Discoveries from this popular wave of PCP research has found its involvement in polarized ciliary beating in the trachea and brain ventricles,[7][8] oriented cell divisions,[9] lung branching,[10] and hair follicle alignment.[11][12]

A major challenge to studying PCP is that the in vivo protein and cell contact signaling required to facilitate it are difficult to recapitulate in a cell culture dish. However, the recent advances in imaging technology and the expansion of genetic tools are helping to uncover how PCP works in the living cell and the role it plays in cell development and biology.[5]

Core Planar Cell Polarity Components

Figure 2: Cartoon representation of Cuticular wing hair defect in Frizzled mutant flies.(A) The structure of Drosophila fly wing with and arrow showing the proximal and distal tips, (B) WT cuticular hairs in normal orientation towards the distal tip of the wing, (C) the disoriented cuticular hairs of the Frizzled(fz) mutant. The structures of the hairs are the same, only the orientation is different. Inspired by the work of David I. Strutt (2001)

Core PCP genes all characterized in Drosophila mutants affect many structures in Drosophila with PCP features including the hair and bristles across the fly body. The core PCP genes in Drosophila and other vertebrates are Frizzled (Fz), Flamingo (Fmi), Strabismus (Stbm)/Vang-gogh (Vang), Prickle (Pk), Dishevelled (Dsh), Diego (Dgo), and trimeric G protein Gαo.[13]

Frizzled (Fz) -The first frizzled mutant in Drosophila was identified in 1982 by D. Gubb and A. Garcia-Bellido. The mutant had polarity defects in the wing, notum, haltere, legs, abdominal tergites and abdominal sternites.[6] Specifically, D. Gubb and A. Garcia-Bellido saw a polarity defect in the cuticular hairs and bristles on the wings. Later research found that the function of the Frizzled (Fz) gene in Drosophila melanogaster is required to coordinate the cytoskeletons of epidermal cells to orient cuticular hairs and bristles on the surface of the insect. “In Fz mutants it is not the structure of individual hairs and bristles that is altered, but their orientation with respect to their neighbors and the organism as a whole.”[14] As shown in Figure 2, in wild-type wing all hairs point towards the distal tip, but in Fz mutants the hairs point in a disordered manner.[14] Frizzled is a seven-pass transmembrane protein and because of this it gives epithelial cells the ability to transmit and interpret polarity information from neighboring cells epithelial.[14]

Flamingo (Fmi) – Another seven-pass transmembrane receptor, Flamingo is also a cadherin that localizes at cell-cell boundaries in the epithelia cells of Drosophila wing. In the absence of Fmi, planar polarity was distorted. Fmi localization at the proximal/distal cell boundary is first dependent on the localization of Frizzled at the same boundaries.[15]

Canonical Vs. Non-Canonical Wnt Pathways and PCP

The PCP signaling pathway includes several components (Fz, Dsh and Gαo) of the ‘‘canonical’’ Wnt signaling pathway. However the core PCP proteins can function independent of β-catenin to result in downstream changes to cellular cytoskeleton and are known as a ‘‘noncanonical’’ Wnt pathway.[13]

Cross Protein Interactions to Establishing PCP Asymmetry

The hallmark of the PCP system is the asymmetric and polarized membrane expression of PCP proteins. Disheveled (Dsh) and Diego (Dgo) are cytoplasmic proteins and are recruited to the membrane by each other and by their association to the transmembrane PCP protein Frizzled (Fz) and cytosolic Disheveled.[13] Strabismus (Stbm)/Vang-gogh (Vang) is a four-transmembrane protein and can recruit cytoplasmic PCP protein Prickle (Pk).[13] It is known that Prickle can interact with Disheveled and perturb its recruitment by Frizzled. Through a feedback loop of the extracellular domains of Frizzled and Strabismus at the junctions of two neighboring cell membranes, the complex of Strabismus and Prickle and the complex of Frizzled and Disheveled and Diego are localized to opposite sides of the cells along the polarization axis.[13] Flamingo (Fmi) is thought to localize to both sides and plays a role in homophilic adhesion, the adhesion of cells by the interaction of similar cadherin types.[13] Failure of these PCP proteins to segregate correctly within a cell boundary can lead to a disruption in PCP such as with the hair cells on fly wings and mouse skin.[13]

References

  1. ^ Kelly, Michael; Chen, Ping (2007). "Shaping the mammalian auditory sensory organ by the planar cell polarity pathway". The International Journal of Developmental Biology. 51 (6–7): 535–547. doi:10.1387/ijdb.072344mk. ISSN 0214-6282.
  2. ^ Park, Tae Joo; Mitchell, Brian J; Abitua, Philip B; Kintner, Chris; Wallingford, John B (2008-06-15). "Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells". Nature Genetics. 40 (7): 871–879. doi:10.1038/ng.104. ISSN 1061-4036.
  3. ^ Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B.; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A.; Murdoch, Jennifer N.; Humbert, Patrick O.; Boulos, Nidal; Weber, Thomas; Zuo, Jian (July 2010). "Epidermal Wound Repair Is Regulated by the Planar Cell Polarity Signaling Pathway". Developmental Cell. 19 (1): 138–147. doi:10.1016/j.devcel.2010.06.008. ISSN 1534-5807.
  4. ^ Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B. (2011-07-15). "Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration". Development. 138 (14): 3033–3042. doi:10.1242/dev.063842. ISSN 1477-9129.
  5. ^ a b c d Devenport, Danelle (2014-10-27). "The cell biology of planar cell polarity". Journal of Cell Biology. 207 (2): 171–179. doi:10.1083/jcb.201408039. ISSN 1540-8140.
  6. ^ a b Gubb, D.; García-Bellido, A. (1982-04-01). "A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster". Development. 68 (1): 37–57. doi:10.1242/dev.68.1.37. ISSN 1477-9129.
  7. ^ Tissir, Fadel; Qu, Yibo; Montcouquiol, Mireille; Zhou, Libing; Komatsu, Kouji; Shi, Dongbo; Fujimori, Toshihiko; Labeau, Jason; Tyteca, Donatienne; Courtoy, Pierre; Poumay, Yves; Uemura, Tadashi; Goffinet, Andre M (2010-05-16). "Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus". Nature Neuroscience. 13 (6): 700–707. doi:10.1038/nn.2555. ISSN 1097-6256.
  8. ^ Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin M.; Scott, Matthew P.; Axelrod, Jeffrey D. (December 2012). "Microtubules Enable the Planar Cell Polarity of Airway Cilia". Current Biology. 22 (23): 2203–2212. doi:10.1016/j.cub.2012.09.046. ISSN 0960-9822.
  9. ^ Gong, Ying; Mo, Chunhui; Fraser, Scott E. (2004-07-14). "Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation". Nature. 430 (7000): 689–693. doi:10.1038/nature02796. ISSN 0028-0836.
  10. ^ Yates, Laura L.; Schnatwinkel, Carsten; Murdoch, Jennifer N.; Bogani, Debora; Formstone, Caroline J.; Townsend, Stuart; Greenfield, Andy; Niswander, Lee A.; Dean, Charlotte H. (2010-03-10). "The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis". Human Molecular Genetics. 19 (11): 2251–2267. doi:10.1093/hmg/ddq104. ISSN 1460-2083.
  11. ^ Guo, Nini; Hawkins, Charles; Nathans, Jeremy (2004-05-28). "Frizzled6 controls hair patterning in mice". Proceedings of the National Academy of Sciences. 101 (25): 9277–9281. doi:10.1073/pnas.0402802101. ISSN 0027-8424.
  12. ^ Devenport, Danelle; Fuchs, Elaine (2008-10-12). "Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles". Nature Cell Biology. 10 (11): 1257–1268. doi:10.1038/ncb1784. ISSN 1465-7392.
  13. ^ a b c d e f g Jones, Chonnettia; Chen, Ping (2007). "Planar cell polarity signaling in vertebrates". BioEssays. 29 (2): 120–132. doi:10.1002/bies.20526. ISSN 0265-9247.
  14. ^ a b c Vinson, Charles R.; Conover, Sharon; Adler, Paul N. (March 1989). "A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains". Nature. 338 (6212): 263–264. doi:10.1038/338263a0. ISSN 0028-0836.
  15. ^ Usui, Tadao; Shima, Yasuyuki; Shimada, Yuko; Hirano, Shinji; Burgess, Robert W; Schwarz, Thomas L; Takeichi, Masatoshi; Uemura, Tadashi (September 1999). "Flamingo, a Seven-Pass Transmembrane Cadherin, Regulates Planar Cell Polarity under the Control of Frizzled". Cell. 98 (5): 585–595. doi:10.1016/s0092-8674(00)80046-x. ISSN 0092-8674.

See also

Cell polarity

Frizzled

Prickle (protein)

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